Dr. Paul Offit Answers Common Questions About COVID-19 Vaccines
Jan 29, 2021

Dr. Paul Offit, Director of the Children’s Hospital of Philadelphia’s Vaccine Education Center, joined Vaccinate Your Family’s Executive Director, Amy Pisani, on Monday, January 25, 2021, to answer questions about COVID-19 vaccines on Facebook Live. Watch the full video here or read the transcript below. 

Amy Pisani:

Hello and welcome to Dr. Paul Offit. My name is Amy Pisani, and I’m the executive director of Vaccinate Your Family. We are here to talk about COVID vaccines and we’re here to take your questions. So, let me introduce to you our wonderful guest speaker. Dr. Paul Offit is a pediatrician specializing in infectious diseases and an expert on vaccines, immunology, and virology. He is the co-inventor of a rotavirus vaccine that has been credited with saving hundreds of lives every day. Dr. Offit is the Maurice R. Hilleman professor of vaccinology, professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.

He’s currently a member of the National Institutes of Health working group on vaccines, a subgroup accelerating COVID-19 therapeutic interventions in vaccines, and that’s comprised of experts to combat COVID-19. He’s also a member of the FDA Vaccines and Related Biological Products Advisory Committee, which for many of you have been following the approval of the vaccines and the authorization of it, all vaccines go through what they call VRBPAC in order to make decisions on vaccines. He was previously a member of the Advisory Committee on Immunization Practices, and he is a Board member of Vaccinate Your Family and the Autism Science Foundation. I’m just going to pause for one second, Dr. Offit, while I make sure that the live feed is working on Facebook. Yes, I do believe we are all set to go. So, Dr. Offit, if you’d like to say hello, and then I’ll ask a couple questions.

Dr. Paul Offit:

Well, Amy, thanks for asking me to do this. Obviously, Vaccinate Your Family is one of the best organizations in the United States and world at educating us about vaccines, so it is an honor for me to be on this program.

Amy Pisani:

Well, that’s really nice to be to say that, Paul. All right, so I have a couple of questions that we’re going to ask you and then we’re going to wait while questions are coming in on Facebook. So everyone is watching the world, we’re starting to get vaccinated. Thank goodness the vaccines have been created and here we are learning more every day. Some people have reached out to Vaccinate Your Family asking whether or not the COVID-19 vaccines, both the emergency authorized mRNA vaccines from Pfizer and Moderna and the COVID vaccine in development from Johnson & Johnson can affect our own DNA. Is that possible?

Dr. Paul Offit:

All right, so I’ll start with the messenger RNA vaccine. Right now we don’t have an approved vaccine from Johnson & Johnson, so I’m going to talk about the two vaccines that we’re currently getting. So what messenger RNA is, I’m going to give you the scientific answer, but I’m going to try and make it simple enough so it’s understandable, and if I don’t, let me know. Messenger RNA is just a small piece of genetic material that instructs cells on how to make proteins.

We all have thousands of copies of messenger RNA in every one of our cells every day because all of our cells make proteins as a way to survive. So, here what you do is you take this messenger RNA and you put it in this lipid nanoparticle, just this little lipid capsule, and then that’s taken up by the cell, the lipid capsule is stripped away, and then you have this messenger RNA in the cytoplasm of the cell.

So, the cell has two compartments, it’s got the cytoplasm, and it’s got the nucleus, and the nucleus has a membrane around it and inside the nucleus is the DNA. So, there are three reasons why it is impossible for messenger RNA to change your DNA. First, the messenger RNA has to get into the nucleus. In order to do that, it requires something called a nuclear access signal, which it doesn’t have. Therefore, it can’t possibly get into the nucleus. Even if it could get into the nucleus, it’s not DNA, it’s RNA. It’s a different molecule. It’s like Spanish and English, two different languages.

So, in order for the messenger RNA to in any way affect DNA, it would first have to become DNA. And, it could do that via an enzyme called reverse transcriptase, which basically makes RNA DNA. It doesn’t have that enzyme. Therefore, not only can it not get into the nucleus, but even if it got into the nucleus, it doesn’t have the enzyme that it would allow it to become DNA. Even if it got into the nucleus, which it can’t do, or even if it was transcribed to become DNA, which it doesn’t have the enzyme to do, even if that all happened, it has to be integrated into the DNA. In order to do that, it requires an enzyme called, not surprisingly, integrase, which it also doesn’t have.

So, for three reasons it is not possible for messenger RNA to in any way affect DNA. You have a better chance of becoming Spider-Man if you’re given a messenger RNA, than you do of having in any sense the DNA be altered by your messenger RNA. Although technically, since we’re trying to stick to the science, you become Spider-Man when you’re bitten by a radioactive spider, just so we’re clear on it.

Amy Pisani:

Great. Thank you, Dr. Offit. I do want to make sure, folks that are live on Facebook, I understand there was a bit of a delay, and so it’ll be catching up, but Dr. Offit was just answering the question about whether or not these vaccines can actually affect your DNA. So again, thank you for joining us, Dr. Offit. You’re a member of our board. I don’t quite know what we would do without you. Your answers are always so helpful, especially to the general public, so here we go.

We’re going to continue seeking questions from Facebook and I hope we can get to as many as possible. So the next question, can you talk more about those variant strains of the COVID-19 virus that we’re hearing about? Are they more likely to cause people to get very sick from COVID? And then secondly, will the COVID vaccines currently from Pfizer and Moderna be able to protect against these new strains? What do we know so far?

Dr. Paul Offit:

Right, so that is the question of the day, definitely. I’ll start from the beginning. In November of 2019, there was a bat coronavirus that became evident in Wuhan, China that made its debut in the human population. It’s a bat virus, it’s not a human virus, and so what’s happened is what you would expect to have happen. The virus is trying to adapt to growing in humans. That’s what it’s doing.

When it does that, it will then create variants. That had to happen, and it’s happened. So, the critical question is not whether there were going to be variants or not, there were going to be variants. The question is, are those variants in any way functionally different from the original strain? And by functionally different, what I mean is more contagious, more virulent, meaning more likely to cause severe disease and worst case scenario, does it start to escape recognition by vaccine-induced immunity?

So, I’ll start with the first thing. There are four prominent variants, which one of which was just recently described in the last few days. The UK variant, which probably most people have heard of, the South African variant, the related Brazilian variant, related to the South African variant, and then just the last few days, the California variant, so four variants. In terms of the question of are these variants more contagious, it does look like the UK variant is more contagious. This has never really been subjected to a formal proof, which is through contact tracing to see that if you’re infected with a non-variant virus, or rather, other people are infected with this variant virus, or you’re infecting more people during the day. It’s never really been subjected to that.

But, there’s enough evidence to suggest that UK variant is probably more contagious, that’s true. In the question of virulence, it doesn’t look like any of these strains are more virulent. Meaning that if you get it, you’re more likely to have severe disease. Because the UK virus is more contagious, therefore, you’re more likely to catch it. Therefore, you’re more likely to get sick. People have tried to argue that it’s more virulent, but if you look at people who are admitted to the hospital in the United Kingdom, who either are infected with a non-variant strain, or infected with a UK variant strain, they are no more likely to die if they were infected with one strain or the other.

So, there’s no evidence that it’s more virulent, no. The critical question, because the only way out of this pandemic is with a vaccine, is have these viruses started to escape recognition by vaccine-induced immunity? That is the critical question, and that is a question you’re going to be hearing about for the next year. Here’s what I would say. The way to answer that question is you want to see whether or not people who have gotten two doses of this vaccine despite that are still getting hospitalized or dying from these variant viruses. So, there’s not that many people in the United States right now who have received two doses. Let’s assume somewhere between two and three million people in the US have received two doses of either the Moderna vaccine or the Pfizer vaccine.

When you start to read about them being admitted to the hospital with COVID-19 and that those hospitalizations are being caused by viruses that are one of these variant strains, that’s a bad sign. That hasn’t happened yet and it may well never happen. So, what we’re trying to do now is to predict whether or not that would happen, but the tools that we have to predict that are imperfect. So for example, with a UK variant, both Pfizer and Moderna have taken the sera, the antibodies that were generated from their vaccines to see whether or not those sera, those antibodies generated by a vaccination neutralize the UK variant, and they do, so that’s good. So the thinking is, that virus is probably not going to escape recognition by vaccine-induced immunity.

With regard to the South African variant, it looks like that both for Moderna and Pfizer there is a lesser neutralizing immune response in the laboratory. It’s not gone, it’s just less, so the problem with trying to make sense of that is you don’t really know what the immunological correlate for protection is. So, even though you have lesser neutralizing antibodies, say, if you’re inoculated with Moderna or Pfizer’s vaccine, take your antibodies from your sera and see whether it neutralizes this South African variant, and you find that it doesn’t neutralize it as well, it still may be well enough to protect you against disease, so you don’t know that yet.

Also, when you’re looking at antibodies, you’re only looking at one part of the immune system. There are other parts of the immune system other than antibodies. There are these specialized cells called T cells, and there are different sets of T cells. There are T cells that help you make antibodies, there are T cells that kill virus-infected cells, both of which are important in getting better from disease and those are never studied in these days, so you don’t know. You don’t know, I think that what we should do is prepare for this, meaning generate vaccines that include these variant virus genomes, that decode for the spike protein, do that, and even consider a booster dose down the line because that may be good enough with just the normal vaccines we’re using now.

But for right now, I think here’s what would be my summary, there’s no evidence that these variant viruses have escaped vaccine immunity clinically, none, not at all. There’s some evidence in the laboratory that they might. And so, we need to be vigilant, we need to be much better sequencing these viruses in the United States. For whatever reason, we’re just not very good at that. The UK is much better at that. When we say, for example, we haven’t seen the South African variant in the US, it’s mostly because we haven’t looked. I think the United States needs to look at many more strains to make sure that’s true. So we need to do that, and we need to make sure that if anybody is ever hospitalized, we’ve gotten two doses of vaccines. We look very carefully at… Meaning with COVID-19, we look very carefully to see what the nature of those viruses are.

Amy Pisani:

So basically, as more and more people are getting vaccinated in our nation, and if they end up becoming ill from this other variant we’ll have a lot more evidence. But right now, it’s basically fingers crossed that the technology will continue to protect us. I think it gets a little bit confusing when we’re trying to teach people about the difference between an mRNA technology and how that spike protein is cut off. The ability for the virus to get into your body through that spike is cut off, versus when you normally use a virus-based technology. I think in my mind that’s where I’m getting confused as to whether or not… Why can’t that basic technology for mRNA just protect you against all variants?

Dr. Paul Offit:

Right, well, it depends. So, when you take that little piece of messenger RNA from the gene for the virus that’s most typically circulating, these non-variant strains. Your body then makes that… The RNA is taken up in your cell, your body makes the spike protein and then your body makes antibodies to the spike protein. It’s a key part of the spike protein, something called the receptor-binding domain. If there’s enough changes in that receptor binding domain with a variant virus, then the antibodies that you’re generating in this virus, neutralizing antibodies you’re generating to the non-variant strain just won’t work. They’re just not going to bind to that region anymore and-

Amy Pisani:

That’s really [crosstalk 00:13:26]-

Dr. Paul Offit:

There are 1,000 amino acids in that and proteins are made up of amino acids. There are 1,000 amino acids in that receptor binding domain region. So, you really have to have a lot of changes there to make a big difference and that hasn’t apparently happened yet, where we can say it’s made a complete difference. This is not flu. Influenza is a moving target. That’s a virus that mutates so much, not just from year to year but frankly from minute to minute that the infection or national immunization the previous year doesn’t protect you, hence the yearly vaccine. That’s not coronavirus, and it’s not even this bad coronavirus. Coronaviruses generally mutate but then mutate slowly. So, I think we will have time here to figure out whether or not this is going to be a problem. This is not flu.

Amy Pisani:

Thanks, Dr. Offit. All right, I want to welcome our friends on Facebook. I know a lot of people are joining as we move forward. So, I have a couple of questions straight from the comments question. So the first one is, is taking acetaminophen or ibuprofen not recommended for COVID vaccine side effects, so as not to stifle the body’s ability to build immunity?

Dr. Paul Offit:

Right, so it’s a great question. So, when you develop fever, so the question is why do we develop fever? Why is it that everything that can walk, swim, crawl or fly on this planet can make fever? Do we do it just keep the makers of Tylenol in business? Probably not. Our body does this for a reason. The reason we do it, the reason we all make fever and this may surprise you is because our immune system works better at a higher temperature. The fact is you have to pay a price for that, a metabolic price for that. It’s not fun having fever. You have headaches, you have chills, you have muscle aches, so you pay a physical price for fever.

You also pay a metabolic price for fever. Your basal metabolic rate increases about 12% for every degree centigrade of fever. So we pay a price for people, which is why we only have it when we need it. There are many studies, probably more than 20, that have shown that if you treat fever during an infection, you actually can often prolong or worsen that infection. So, we try to avoid treating fever in our hospital for that reason. So then the question becomes, well, how about vaccines? If you give a fever reducing medicine before you get a vaccine, will that reduce your immune response to the vaccine?

There’s two big studies on this. One was in Australia, the other was in the Czech Republic. One was just looking at flu vaccine, the other was looking at a variety of pediatric vaccines. And, both studies found that if you pretreat with anti-fever medicines like Tylenol or ibuprofen before you get a vaccine, you will lower your immune response. So, I would say don’t do that. There’s less inflammation and what happens if you’ve already developed symptoms. This isn’t an easy vaccine, these mRNA vaccines. You can often have about 50% of time, you can have fever, typically low grade fever, but sometimes higher, and then chills, body aches, joint pain, fatigue. I’ve had my second dose of vaccine. With the first dose, I had about 10 hours of fatigue and low grade fever. With a second dose, I like two days of fatigue and fever.

So, the good news is I lived and also I now am comfortable that I have an immune response that is going to protect me. It’s just your immune response working, although we always use terms like side effects and adverse events. It’s just your immune system working. The story I tell because I think it’s perfect is there was a friend of mine in North Carolina, who was part of the Pfizer trial. So, he didn’t know whether he got a vaccine or he got a placebo. After the second dose, the next morning he wakes up, he has fever and he’s fatigued. He looks at his wife and says, “Yes, I got the vaccine.” That’s the right attitude.

Amy Pisani:

That’s funny. Well, fever definitely has a purpose. I have a girlfriend who has got her second dose this weekend and she said her teeth were like those windup chattering things that they wouldn’t stop chattering, but she’s a nurse, and she knew what was going on, but now she’s protected. Second question, what is the current evidence, if any, about the new vaccine’s effect on transmission? What do you expect to see on this issue?

Dr. Paul Offit:

So the little we know, we know that when Pfizer did its trial of 44,000 people or Moderna did a trial with 30,000 people, what they both showed was that those vaccines could prevent disease, mild, moderate, or severe disease. What they didn’t show was whether or not you could protect against infection where you’re infected, but you don’t have disease. You just can shed virus, you can still be contagious, you’re infected, you’re contagious, but you’re not sick. Can this vaccine prevent that? I really think this is much ado about nothing and here’s why. I think that it is likely that if you’ve been vaccinated, although you may still get infected and shed virus, you will shed less virus than someone who’s not vaccinated.

There’s abundant evidence for that with other sort of vaccines. The rotavirus vaccine, the vaccine that I was fortunate enough to be part of at Children’s Hospital in Philadelphia does not protect against asymptomatic shedding. But, babies and children who are infected a second time, shed less virus. And the fact is, we were able to virtually eliminate the virus from the United States, even though it’s not a vaccine that prevents asymptomatic shredding. So, I think that even if it doesn’t protect against asymptomatic shedding, I think you would shed less, and I think it doesn’t matter. I think we still would be able to eliminate the virus from this country even if we don’t do that.

Now, the CDC has recommended largely for this reason that even if you’ve gotten two doses of vaccine, wear a mask, physically distance, because you don’t know whether you’re asymptomatically infected. But for me, the main reason that I still wear a mask and socially distance is not that, it’s that the vaccine’s 95% effective, it’s not 100% effective, I may be one of those one in 20 people who could still get sick. So, that’s why I still wear a mask and physically distance and I think until we get control of this virus, until we’ve shown that the contagiousness index has dramatically dropped and we’re seeing far fewer cases and hospitalizations and deaths, until that happens, I’m still going to wear a mask and social distance.

Amy Pisani:

So, when you talk about wearing a mask, I think there’s a bit of confusion. I have to tell you, I ran into a woman the other day who was a senior and she wasn’t wearing a mask in our building and I said, well… She said, “I got vaccinated.” And I said, “Oh my gosh, let me just explain a little bit about herd immunity.” And she asked me what it is I did, and so I brought her in my office, gave her a mask. So, let’s just say you’re in a group of people, say you’re part of a club, you’re part of Rotary — I love Rotary — and everyone in my Rotary Club is vaccinated. Say it’s May. Does that count as 100% community immunity, or do you still need your whole town, your whole state vaccinated in order for that to be in effect?

Dr. Paul Offit:

It depends on who surrounds you. There was a study done in the Netherlands in the late 1990s about measles, and the result is going to surprise you. But when you think about it, it’s not surprising. You were much better off being unvaccinated living in a highly vaccinated community, then being vaccinated and living in a highly unvaccinated community because no vaccine’s 100% effective. If you’re much more likely to be exposed, then you’re much more likely to get sick and this with measles. A measles vaccine, two doses of measles vaccine confers 97% protection for the rest of your life and it’s sterilizing immunity, meaning you’re protected against disease, you’re protected against infection. Still, you’re at risk being vaccinated, living in a relatively unvaccinated community.

So, you’re only as good as the people around you, and you don’t know their story. And, if you walk outside, assuming you walk out, you take the risk of walking outside, even if you’re vaccinated, no vaccine’s 100% effective, and you don’t know who you’re coming in contact with. So, I don’t think people should feel like there is this shield of armor around them. I think they can feel better and I do feel better. Yesterday morning, I went to the services with my son and I’m always a little nervous about doing that. But this time, I was much less nervous because I was vaccinated, but still, I wore a mask and physically distanced.

Amy Pisani:

That must be a great feeling, I can’t wait. Here’s one that we hear a lot here actually, how do you explain to people in simple terms that this vaccine won’t cause sterility or inability to carry a fetus?

Dr. Paul Offit:

Right, so first as a general rule, vaccines don’t do things that natural infections don’t do. So for example, SARS-CoV-2 is a common infection in the United States. We listed now the 25 million people who have been infected, but that number is low. That 25 million number, there are people who have been tested and found to be infected. If you do antibody surveillance studies where you can, in much more sensitive way, figure out who really has been infected, that number of 25 million is probably off by a factor of three. So, it’s probably closer to 70 million people who’ve been infected in this country. That’s 20% of the population. Many of those people who are pregnant, and so the first question is, are people who are pregnant who are infected with SARS-CoV-2, one, are they more likely to miscarry? No. Two, are they more likely to develop babies who have abnormalities, so called congenital abnormalities? No.

So, the natural infection doesn’t do that. There’s no reason to suspect that the vaccine, which is only one protein from that virus, the virus has four proteins, it’s only one protein from that virus would ever do that. So, it doesn’t make sense that would ever happen. Now, you don’t have a lot of information. In the Pfizer trial, there were 23 women who became pregnant during that trial. In the Moderna trial, there were 13 women who became pregnant. This is roughly almost 40 women total who became pregnant during those trials. And obviously, half got vaccinated, half got placebo. There were no problems in the trial, but I really applaud the CDC to do something I would have never imagined they would have done, which is that usually when you don’t have data, because it’s unfortunate actually, I think we should include pregnant women far more in these trials than we do, rather than excluding them.

But, what they did was usually we don’t have a lot of data to say that something is safe, not because it necessarily might be unsafe, just because you don’t have the data, they’ll make it a contraindication. They’ll say, “Don’t get this vaccine if you’re pregnant.” Here, they actually said that a woman could reasonably get the vaccine if pregnant and the main reason is, is that if you’re pregnant, and you’re infected with SARS-CoV-2, you are more likely to suffer severe disease than if you’re a woman of the same age who isn’t pregnant. So, you’re protecting yourself and you’re also actually generating antibodies, which you will passively transfer to your baby for the first few months of life. So, there’s really every reason to get vaccinated. Were my daughter pregnant, I would recommend that she… And, if she was deciding whether they get the vaccine, I would recommend that she get it.

Amy Pisani:

That’s good to hear. It’s the same as flu, right? We know that vaccinating against flu and pertussis during pregnancy will help protect the newborn. I think for some people, COVID hasn’t been such a disproportionately frightening disease for children and we’re lucky in that realm, but I think that that’s why people are a little bit confused I think, because we know with flu, it’s so dangerous to get flu as a pregnant woman, but also children are at greater risk. So, I think that that balance is a little bit more confusing here. One thing I would mention though, is the CDC is meeting on the 28th, one of their emergency meetings, and I would say that people should watch that, the ACIP meeting. Thousands of women now have been vaccinated that are pregnant. And so, I’m continuing to go with that data and I always appreciate that they’re willing to do that. You showed me-

Dr. Paul Offit:

I think the meeting is on the 27th, but you’re right [crosstalk 00:25:27]-

Amy Pisani:

Sorry, yes. My sister’s birthday is the 28th. My sister Betsy, who’s watching. Okay, here’s one. So, is there any concern that being… Sorry, I just mushed it off. Is there any concern that being vaccinated might cause antibody-dependent enhancement when challenged with one of the variety viruses, particularly the South African, Brazilian variant?

Dr. Paul Offit:

I should explain what antibody-dependent enhancement is. The best example of that would be a virus called dengue virus, which is not a problem in the continental United States. It’s a problem in Puerto Rico and many areas of the world. Dengue is a very common virus that causes tends of thousands of people to die every year. There are four different types of things of dengue, four different so-called serotypes of dengue. It’s odd and that if you’re infected with one strain of dengue, and then you recover, and then you’re infected with a different type of dengue, a second different type, you actually do much worse than if you’ve never been infected before. It’s called dengue hemorrhagic shock syndrome and is as bad as it sounds.

It’s an overwhelming disease associated with shock hemorrhage, which is a bleeding disorder. So, you’re worse off having been naturally infected with one type of dengue and then being infected again with a second time. What happens there, excuse me, is that when you’re infected with the first type, you develop neutralizing antibodies to that type and binding antibodies to the other three types, but not neutralizing. Neutralizing is good, neutralizing means the virus can’t enter in the cell. Binding antibodies doesn’t mean that at all. So, now you’ve got binding antibodies against the other three types. Now, you’re infected with this second type, so that your antibodies, they don’t neutralize the virus, they just bind to the virus and that actually serves as a Trojan horse that allows the virus to enter the cell through something called the Fc receptor, but that’s what happens.

The binding antibodies actually allows the virus to enter the cells more easily and that’s why it’s a more severe infection. This came up with SARS-1 that in experimental animal models, it looked like if you were infected with SARS-1 and then reinfected, that you actually had what appeared to be antibody-dependent enhancement. That is not true with SARS-2. It’s not true in animal models, it’s not true in animals that get a SARS vaccine and then get infected with SARS. It’s not true in animals that get a SARS virus, natural virus and then get infected again, it doesn’t happen. It’s not true in people who get convalescent plasma who were sick, which is another way of looking at it. It’s not true in anybody who’s gotten the vaccine. So, I think there are many reasons to think that this is not going to be a problem here. It was always worrisome because of what happened with SARS-1, but there’s too many reasons now to believe this is not going to be an issue for SARS-2.

Amy Pisani:

So another question, a scientific question, can you talk about the antibodies and the principal correlative protection, and why is there reluctance to use antibodies as that indicator of protection?

Dr. Paul Offit:

Right, of interest, so what an immunological correlative protection is, it is to say… So, if I get a SARS-CoV-2 vaccine, and I look at my bloodstream and find that I have antibodies in my bloodstream that neutralize that virus at a certain level, either geometric mean titer, or dilution, whatever measure you use, and I say if I’m above that level, I’m protected. I know for sure I’m protected. That is an immunological correlative protection. We don’t have that yet for this virus. And frankly, for many of the vaccines out there in the market, there’s not a clear immunological correlate for protection. It makes life a lot easier to have one, but we don’t have one yet.

The place where you can often find it is in those vaccine trials, not the people who got the vaccine and were protected, the people who got the vaccine and weren’t protected, the so-called breakthrough cases, of which there were eight in the Pfizer trial and then 11 in the Moderna trial. So, that was 19 people who got a vaccine, but despite getting that vaccine still weren’t protected.

Well, you would love to know because we have those sera, when you look at those sera, did they have lower levels of antibodies as compared to the people who were protected? And as yet, neither of the companies have said what those data were. It’d be nice to see them. It’s not that hard to do those studies, but my suspicion is those people may have had the same antibody response as the people who were protected. In which case, you’re not going to have a clear immunological correlate. Now, that was only like 19 people, so you really need at least 35 or 40 people to make any sort of reasonable statistical statement. So, I think it may take us a while to figure this out.

It would help to know that, but right now, we don’t have a correlate, which goes back to the original question about these variant strains. When they look at neutralizing antibodies in the sera of people who were vaccinated, and then say, well, there was somewhat of a reduction in the ability of those antibodies from people who were vaccinated to neutralize these variant strains, you don’t know what that reduction means because you don’t have any immunological correlate yet. So, we should stop scaring ourselves right now, which we’re very good at doing with this virus because right now, you don’t know that this is escape vaccine recognition.

Amy Pisani:

So, talking a little bit more about natural virus when you get COVID as opposed to… We usually talk about vaccines, just a couple questions that I’ve heard from friends recently because I know people now keep getting the virus. So, you get the virus and now you’re technically immune. We don’t know how long that lasts for, but the bigger question people are having is, so you get the virus and then you go and get a COVID test and your COVID test comes out negative, why would that happen?

Dr. Paul Offit:

You mean antibody tests or-

Amy Pisani:

No, an actual COVID test.

Dr. Paul Offit:

Antibody test?

Amy Pisani:

No, you have COVID, and then two weeks later you go to get a COVID test, nasal swab, PCR test, it comes back negative.

Dr. Paul Offit:

Got it.

Amy Pisani:

Can you explain that?

Dr. Paul Offit:

Right, so when you’re infected with a SARS-CoV-2 virus, you for the most part will shed infectious virus for about six days or seven days roughly, and then you stop shedding infectious virus. Interestingly, you can still be PCR positive for three months or longer. The PCR, which stands for polymerase chain reaction is just a way to detect the virus gene, even small fragments of the virus gene. It’s a very sensitive test, in many ways too sensitive because it doesn’t really tell you whether you’re shedding infectious virus anymore. When you’re PCR positive, that just means that you were infected at some point in your life. If you’re PCR negative, great. You’ve rid yourself not only of the virus, but even any evidence of the viral genome. It’s a weird virus from a virologist standpoint, from a nerdy virologist standpoint, or said another way, my sampling, it’s a weird virus because why would… The virus genome is messenger RNA, that is what the genome is.

Messenger RNA is a very labile molecule. It breaks down very quickly on mucosal surfaces, like your nose or throat. So, why is it that you’re PCR positive for three months, but you’re only shedding infectious virus for a week? What that means is that the virus is continuing to make genome, but it’s not making whole virus anymore. Why would a virus do that? This is a very weird virus. It’s been weird right from the moment it came out of Wuhan, when it was billed as a winter respiratory virus. It is far more than that. It’s far more than just a respiratory virus as we’re learning the hard way. It causes inflammation in blood vessels, even though it doesn’t enter the bloodstream and with that inflammation of the blood vessels, otherwise known as vasculitis, it can cause strokes, it can cause heart attacks, it can cause kidney disease, it can cause liver disease. It causes this multi-system inflammatory disease in children, which I haven’t seen before, not like this. It’s unique in that way.

It clearly disproportionately affects people who are older. I think like 40% of the deaths are in nursing homes, but 92% of the deaths from people over 55. It affects your sense of taste and smell, sometimes for months. It’s been detected by neuropathologists and some people in the brain. This respiratory virus does this. It was billed as sort of a pneumonia virus like flu. It is not that and that’s why it’s scary, frankly. That’s the most scary part is that it causes vasculitis.

Amy Pisani:

And I think you’re right, it’s really scary when people are weighing, do I want to get vaccinated? What are the long term effects of getting vaccinated? We know vaccines, they are very safe and they don’t tend to have long-term side effects. We have no idea how bad the side effects are going to be in the long-term from actually getting COVID. Sure, lots of people are getting it and they’re surviving, but we don’t know what’s going to happen five years down the road.

Dr. Paul Offit:

Right, these long haulers Obviously, I think that represents a variety of things. I don’t think it’s one thing that causes long haulers, but you worry that the vasculitis, the inflammation of blood vessels is causing more long-term problems. That’s what scares me the most about this. That’s why I couldn’t wait to get the vaccine is because of this ability of the virus to affect your blood vessels and it doesn’t even enter your bloodstream. It does it by inducing an immune response directed against the cells that lie in your bloodstream, so called endothelial cells. That’s how it works. The other thing it does, which is again, completely weird, there were two papers in science that went through this, is it actually can induce you to, especially men, can induce men to have have antibodies against one part of their immune system, so called the interferon I system, which is why it is a class size of men do worse than women, although men always do worse than women with infectious disease because, Amy, as you know, we are the weaker sex.

Amy Pisani:

I do. Well, you said it, not me. Okay, so-

Dr. Paul Offit:

[crosstalk 00:35:41] silly little Y chromosome. I think she’s the one who said it best.

Amy Pisani:

Let’s talk about children for a little bit more. What do we need to know before we determine that the COVID vaccine is safe for children under 12? What’s going on with the studies on that?

Dr. Paul Offit:

Right, so there’s an interest in all companies really looking at children, which is a good idea. I think that if you take a step back, and you look at people less than 21, comprise about 26% of the US population, but only 0.08% of the deaths. Nonetheless, children can die from this disease. And frankly, the number of children that died this past year of COVID-19, is roughly the same number of children who died of flu, about 150, 160 children or so, and for whom we also recommend a vaccine. And it’s not just death. They can be hospitalized with pneumonia, including severe pneumonia. They can certainly get this weird sort of multi-system inflammatory disease. At our hospital, that’s what we see the most. We see this multi-system inflammatory disease, which can be debilitating.

So, if a virus like this one can cause children to suffer, and be hospitalized and occasionally die, and you can find a way to safely prevent that from happening, then you should do that. So, I think we do need a vaccine, but children aren’t little adults, we need to do the kinds of studies in children to find out that the vaccine is safe, and that we have the right dose. I think what’s going to happen over the next four or five months is that you’re going to see Pfizer and Moderna and Johnson & Johnson, and the AstraZeneca group, look at children younger and younger, sort of work their way down the list. So now, for example, the Pfizer vaccine is approved for children over 16 and Moderna over 18, but they’re both sort of working their way down list, 12 to 18 years of age, probably 10, so you’ll start to see that work down the list.

And, I don’t think they’re going to be efficacy trials because children don’t… It’s hard to find a lot of children who get very sick with this. So, you would have to do huge efficacy trials to show that you were prevented against disease. So, I think what you’re going to see more is just so called phase I studies, which involve maybe 20 to 100 children, where you make sure you have the dose right that works, where you induce a good immune response, and you make sure you have the dosing interval, so you see that. Then, once you think you have the dose, and once you think you have the dosing interval, then you go to so called phase II studies with hundreds of children, maybe a few thousand children to make sure you can consistently and safely induce an immune response and I think that would probably be enough to get authorization through, again, emergency use authorization for children as a guess. That’s my guess. I don’t know this for sure. I’m just taking a guess.

Amy Pisani:

Well, while we’re talking about the new vaccines, so what are you seeing with the preliminary data from J&J and AstraZeneca? Do we think they’re going to be as effective as mRNA or we don’t know yet?

Dr. Paul Offit:

I haven’t seen preliminary data from Johnson for phase III.

Amy Pisani:

When do you think we’re going to see that data? Do you have any idea?

Dr. Paul Offit:

Well, according to the reporters who call me and ask me to get ready because they think that there’s going to be a data release from Johnson & Johnson, what they really mean by that when they say data release from Johnson & Johnson, what they really mean is there’s going to be a press release from Johnson & Johnson. We’re not going to see this in a scientific paper for a while. So, you read what the company wants you to read, and so that’s not enough. What I love about being on the FDA’s Vaccine Advisory Committee is that we get two briefing documents. The first is the EUA submitted by the company, which is usually 80 to 100 pages long, and goes through the data as they would like you to see it. Then, you get another briefing document from the Food and Drug Administration, who’s gone through all of the clinical data, and they too present all of the data.

And so, you have these two roughly 80- to 100-page documents you can go through that gives you all the information you need, I think, to determine whether or not you feel comfortable with whether these vaccines are safe and effective. And frankly, even though it’s through an emergency use authorization, it really doesn’t matter. I evaluate these data as to all the members on that committee as if it was just a licensed product. The question you’re answering is the question you answer for any licensed product, which is would I take this vaccine myself, would I give this to people in my own family, people I love, and if so, then you recommend it for other people and who they love. So, it really doesn’t matter really, whether it’s under in the EUA or not.

Amy Pisani:

I think that’s really important because that’s the bar that we all in public health go by. I wouldn’t recommend it for my family if I didn’t trust it, and I appreciate your saying that, being a part of this prestigious committee, and I guess… So, what you’re saying is that the emergency use authorization, would you say it’s really just a way that they can overcome all the red tape that’s required for a full authorization, but otherwise, you’re saying that the safety profile has been met the same as it would be for a regular?

Dr. Paul Offit:

Here’s what I would say, the safety profile is as it would be for any vaccine, which is to say you need two months of data after dose two because if you look at what had been serious adverse events associated with vaccines, the vaccines are no different than any medical product, any product that can cause a good response can also cause a bad response, but when you look at those things in the past 100 years, where there has been a serious adverse event associated with a vaccine, it invariably occurs within six weeks.

So, if you have two months of data on tens of thousands of people, that makes me feel very comfortable about safety. The reason these aren’t licensed products really has to do with efficacy. You would not get a license to show that a vaccine is 95% effective for three months or four months, you wouldn’t do that. You would have to have a few years of data. The size of these trials, 30,000, 44,000, is the size of any pediatric vaccine trial, HPV, human papillomavirus was a 30,000 person trial. Conjugate pneumococcal vaccine was a 35,000 person trial. These trials are the same size. The difference is the HPV trial was a seven-year trial. The conjugate pneumococcal vaccine was a few year trial. So, we’re not going to do that here. You’re not going to see whether or not the effectiveness you see after three to four months is also true one year later, two years later, three years.

You’re not going to do a two or three year trial for a virus that’s just killed 400,000 people. You’re going to rather say, okay, I have three or four months worth of data, it’s highly effective. Plus, I know I can appear to be able to do so called memory immune response suggesting longer lived effectiveness. Do I feel I’ve mitigated the risk regarding effectiveness enough to put the vaccine out there? And, I think they’ve made the right decision, yes, we’ve mitigated that enough. You’re not going to do a three-year trial before you release this vaccine knowing 400,000 people died this year. You can’t do that.

Amy Pisani:

Right. All right, I’m going to rapid fire a bunch of questions at you about the effectiveness. Is the Moderna vaccine less effective for those over 65 than the Pfizer vaccine?

Dr. Paul Offit:

Those numbers are close enough where I wouldn’t make that distinction. So, one was like 95%, one was 86%, they’re close enough, I think, that I don’t distinguish those two.

Amy Pisani:

What are the implications of today’s Merck news on the other COVID vaccines that are based on viral vector technology?

Dr. Paul Offit:

That Merck’s dropping out, that news?

Amy Pisani:

That news.

Dr. Paul Offit:

It’s disappointing. Merck had a couple strategies that they were at least talking about working on. One was a replication-competent virus called vesicular stomatitis virus, which is a fancy name for a virus that doesn’t really cause disease in people, and they had a lot of experience with that vaccine in stopping the Ebola outbreak in West Africa. So, there was commercial experience with that vaccine. So, it’s too bad that they dropped out. They were also talking about sort of re-engineering a measles vaccine that would then express this SARS-CoV-2 spike protein, but then they’ve dropped out. So, that’s too bad because frankly, the more the merrier. The more companies that are making these vaccines, the better off we are because we are having trouble mass producing them.

Amy Pisani:

What happens if we are lucky enough to get the first dose, the primer, but cannot get the second booster because we’re having a problem with production? Is the effectiveness overall diminished?

Dr. Paul Offit:

One dose is not enough. This is a two-dose vaccine. If you look at the phase I data, your first dose gives you a certain level of neutralizing antibodies and your second dose gives you a dramatically higher level of neutralizing antibodies, plus it gives you so-called T cell responses, which is indicative of memory. So, I think if you’re saying what’s going to give me longer-lived and more complete protection, it is a two-dose vaccine. So, I think when the Biden administration first talked about just getting as much first dose out there as they could, that was the most generous thing I can say about that. It was a messaging problem. It made it sound like one dose was good enough and you had people like Ashish Jah and Bob Wachter writing op-eds in the Washington Post and getting on national television and saying, “Let’s get as many people a first dose as you can.”

Now, if you get the Pfizer doses, a second dose is given three weeks later, the Moderna dose about four weeks later, there is some protection during that period of time. We learned that from those trials because we had people who got dose one and then some people got sick before they got dose two. Were you more likely to get sick if you got placebo than vaccine? Yes, so the Pfizer trials got 52% efficacy in that three week period of time. In the Moderna trials about 80 to 90% efficacy in that four week period of time, but all that told you is that you’ll have protection for a few weeks. It didn’t tell you whether or not you had protection longer than that and given what we learned about the memory responses, the expectation would be that it wouldn’t be much longer than that.

I think what’s happening now is that you’re seeing what happens when we can’t make enough vaccine. So, the CDC is trying to figure out how to make people comfortable that in the situation when there’s not enough vaccine. So if for example, you’ve gotten the first dose of… Well, if you’ve gotten one dose, how long can you wait? So, they’re arguing that you can wait six weeks later. So, that would mean three weeks after you should have gotten the Pfizer vaccine, and two weeks after you should have gotten the Moderna vaccine. That’s probably fine.

I think we don’t know, we haven’t done studies, but I think that’s probably fine. What I worry about is people are going to think, huh, 80% after dose one? I read that in the Washington Post. I heard that on the news, I’m good. 95% after two doses, 80% after one dose, I’m good. No, you’re not good. [crosstalk 00:45:51]-

Amy Pisani:

You’re not good.

Dr. Paul Offit:

There’s really data now are showing that one dose is not enough. You’re starting to see outbreaks with that one dose. So, you need two doses. Do everything you can to get that second dose. You never have to start the series over again, but you’d like to get it as soon as possible. The CDC is saying we are willing to draw the line at six weeks because people are panicking. The other thing is mixing the vaccines, that I’ll get Pfizer the first time and now I can’t get Pfizer anymore. I can only get Moderna. Can I get that second dose as a Moderna vaccine? And, the CDC has relented on this. Initially, their feeling was the right one. We don’t have any data on this, and although these are both mRNA vaccines, they are different molecules. How do you that? Because they’re given at different doses. One is given a 30 micrograms, the other is given at 100 micrograms. They are different molecules.

Now, there’s every reason to believe that one would boost the other. So again, CDC is saying in the world of risk, I think this is a small one, I’d rather get as many people that second dose as we can. So, we’re going to we’re going to make that recommendation. This is what happens when you don’t make enough vaccine is you are just… You don’t have scientific evidence to make these kinds of statements the CDC is making, but they’re trying to do the best they can. What we need to do is figure out a way to mass produce this vaccine, mass distribute it and mass administer it and what I want to hear from the Biden administration now that they have a war on COVID-19, I want to hear from the war room every day and the good news is according to today, the White House has said that starting on Wednesday, we are going to hear from the COVID-19 group daily and that’s great because these people are great.

We don’t have to deal with a Scott Atlases anymore who tell us basically just get infected, and hopefully you won’t die and we’ll get herd immunity that way. That was bad advice, or use hydroxychloroquine, bad advice. So, now you got Rochelle Walensky as head of the CDC, she’s great.

Amy Pisani:

Don’t you have a book called Bad Advice?

Dr. Paul Offit:

I do, yeah. [crosstalk 00:47:40] my book called Bad Advice. Didn’t that sound like a good idea?

Amy Pisani:

It’s great. In my pile of Paul Offit books.

Dr. Paul Offit:

There she is, very good.

Amy Pisani:

All right, I’m going to pull you back in. Get your second dose, that was the key there. We’re talking about policy here. For me, we’re moving on to open it up to more than 75 and older to the younger ages, but there’s so many at-risk people, the phones are going off the hook here at Vaccinate Your Family with just seniors who don’t know how to get their vaccine. They don’t know where to enroll, they don’t know how to get online, they don’t know who to call. And, I think if we just keep barreling over and vaccinating just every generation without bothering to really hone in on the really high risk, elderly population, we’re going to see those deaths continue and it’s really unjust.

So, we got to focus our energies on making sure we don’t miss the highest risk groups, disparate communities. That’s my soapbox, but I’m going to go back to the questions. So, we have four more questions for you. Given the limited amount of vaccines… Oh, we just talked about it. Should the high-risk ones get it first? Yes, we do believe that would be true, correct? If you have a mild upper respiratory infection, not COVID, Can you get the vaccine or should you cancel your vaccine appointment and wait?

Dr. Paul Offit:

I think you can and it’s true for all vaccines really, as long as you don’t have a severe infection, meaning high fever, meningitis, pneumonia. I think if you have a mild upper respiratory tract infection like a cold virus, I think you can still get this vaccine.

Amy Pisani:

What if you have an autoimmune disorder, should you get vaccinated?

Dr. Paul Offit:

That is not a contraindication to getting this vaccine.

Amy Pisani:

And, why would it be important to get a COVID-19 vaccine or any vaccine, really, if you have an autoimmune disorder?

Dr. Paul Offit: 

Well, it depends. If you’re receiving biologicals that in any way weaken your immune system, and usually there’s very specific like HUMIRA, et cetera. That shouldn’t affect your ability to make an immune response, and you’re still recommended to receive the vaccine, but you may be at greater risk for severe disease if you didn’t get the vaccine.

Amy Pisani:

So, people who have cancer should get the COVID-19 vaccine?

Dr. Paul Offit:

Assuming they’re not on immunosuppressive therapies that would affect their ability to make an immune response — yes, absolutely.

Amy Pisani:

Can you talk a little bit about… In the early days, we were hearing a lot about the anaphylactic shock that people were dealing with. How are we doing on that? Have the numbers gone down? What’s going on with that?

Dr. Paul Offit:

So, it’s a background rate in general, there’s like one case of anaphylaxis, which is a severe immediate allergic hypersensitivity reaction. It occurs typically within 15 minutes of getting a vaccine. It’s scary. You can have low blood pressure and sort of feel faint and want to lie down and shock-like symptoms. It’s bad, but the good news is easily recognizable, happens within typically 15 minutes, and it’s easily treatable with a shot of epinephrine. So, that’s why you have to wait for 15 minutes after you’ve gotten a dose of this vaccine, or if you’ve ever had a previous past history of severe allergic reactions, you wait for 30 minutes. What we know now is that for the Pfizer vaccine, it’s roughly 11 cases per million, so it is higher than the background rate for other vaccines.

For the Moderna vaccine, the data that just came out is it’s a little less, about 2.5 cases per million. So, it’s about a quarter of what was being seen with Pfizer. That may change over time, but for right now, those are the rates.

Amy Pisani:

I think I’m just going to ask you just two more questions. What would you say to people who, it was all about the warp speed, and now we’re seeing the vaccines have been created, and now people are clamoring because there’s not enough production? Would you say that there was enough research? I know you got yourself vaccinated. Do you feel like the vaccine had enough research and is safe to get for the general population?

Dr. Paul Offit:

Yeah, first of all, mRNA vaccines are not… The notion of mRNA technology is not new. It’s been 15 years in the making. The people that were the inventors of the mRNA technology are actually UPenn, Drew Weissman and Katelin Kariko, so it’s been worked on for a while. The reason it was so fast was that basically the government took the risk out of it for vaccine makers. They paid for phase III trials, they paid for mass production at risk, those things happen concomitantly. Normally, that wouldn’t happen. Usually, you go phase III trials, show that it works, then you mass produce it. Here, the government said, “We will make this vaccine. We’ll make millions of doses of this vaccine and if it doesn’t work, or it’s not safe, we’ll throw it away.” No company would ever do that, so that’s why it was so much faster.

But no, I think that the only difference really is that the length of the studies for efficacy was shorter than it would be typical, but the size of the trials was typical. So, do I feel that enough work was done to make me comfortable that this vaccine was not rushed into production or use? No, I don’t think that happened.

Amy Pisani:

So, what do you anticipate we’re going to see in the coming weeks with regard to the new vaccines? Let’s say we’re in February, March, do you think we’ll have more production?

Dr. Paul Offit:

Yes, I think that has to happen. If you if you think… Let’s assume you want to vaccinate 70% of the population. All right, so a population of roughly 330 plus million people. So 70%, let’s say around 250 million people, it’s a two-dose vaccine, that’s 500 million doses. If you want to give 500 million doses by the summer, which is to say, five, six months from now, you need to give 3 million doses a day. So, the 1 million doses a day is a floor. We have to do better than that. If we’re getting 1 million doses a day, and we’re trying to get to 500 million doses, we’re talking about the middle of next year, or the end of next year, by the time we finally vaccinated enough people, and that’s not good enough.

We have to do much better than that and I think right now the problem is production. We need to mass produce this vaccine. I think the mass immunization is getting in place in many places. Now, you have mass immunization centers that don’t have the vaccine. So, we need to figure out how to mass produce. The other thing is we really do need to hear from the government and we will. Starting on Wednesday, they’re going to have daily briefings and that’s great because I would like people to ask them the questions, how are you planning to vaccinate 3 million people a day?

Amy Pisani:

And let’s just remember, it’s 3 million high-risk community areas. Let’s not just vaccinate people who are clamoring for it. We’ve really got to make an effort to talk about the vaccines and the competence and reach those communities of color that have been disproportionately been killed by COVID, and I think we’re getting… We talked about it so much in the beginning, the National Academy of Medicine created a great protocol, and CDC pushed that protocol, the timing, the phases, and it seems to have all gone awry, and I think we need to reel it back in and say we don’t want anybody to fall through the cracks. It would be really a disgrace, so I have high hopes. I’m going to have a little bit of fun at the end.

Vaccinate Your Family has these awesome masks. We have these and we have another version. We also have sweatshirts and t-shirts, and I wear them to work almost every day. I’m so lazy lately. So, Jen’s going to put a link to our Bonfire account on the Facebook page. We would love for people to buy them. It is a charity event for us. We do make some funds off of it, not very much. We just mostly want to get the word out. So, Dr. Offit, to thank you, I will be sending you a t-shirt and a couple masks for your lovely family, so please give them our best. We can’t thank you enough. You just took an hour out of your day and I know you’re on the news and just really working non-stop. So truly, thank you on behalf of everyone at Vaccinate Your Family, on behalf of the board, and I will go on to speak on behalf of Mrs. Carter, she thinks you’re one of the greatest people on earth, so thank you for what you do. Have a great day and stay well.

Dr. Paul Offit:

Thank you very much. Thanks for asking me.

Amy Pisani:

Bye everybody on Facebook.

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